Zoledronic Acid Combined with Radiotherapy for Bone Metastases of Malignant Tumor: A Meta-Analysis_Chinese Journal of Evidence-Based Medicine

Authors：

SHI Hongping ^1,2 , ZHANG Qiuning ³ , LIU Guoqing ² , ZHANG Zhigang ^1,2 , WANG Daoying ^1,2 , LIU Xiaofeng ^1,2 ,  WANG Xiaohu ^1,2,3

1. Evidence-Based Medicine Center, Lanzhou University, Lanzhou 730000, China;2. The First Clinical Medicine College, Lanzhou University, Lanzhou 730000, China;3. Gansu Province Tumor Hospital, Lanzhou 730500, China;

Corresponding author：

WANG Xiaohu, Email: xhwanggs@yahoo.com.cn

Keywords：

Radiotherapy; Zoledronic acid; Bone metastasis; Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.20130152

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective 　To systematically evaluate the effectiveness and safety of zoledronic acid combined with radiotherapy in treating bone metastasis of malignant tumor.
Methods 　Such databases as PubMed, EMbase, The Cochrane Library (Issue 10, 2012), CBM, CNKI, VIP and WanFang Data were searched to collect randomized clinical trials (RCTs) on bone metastasis of malignant tumor from inception to October, 2012. References of included studies were also retrieved. Two reviewers independently screened studies according to exclusion and inclusion criteria, extracted data, and assessed the methodological quality. Then, meta-analysis was performed using RevMan 5.1 software.
Results 　Twenty nine trials were included involving 2 021 patients. The results of meta-analysis showed that, compared with the radiotherapy alone group, zoledronic acid combined with radiotherapy improved the effectiveness rate of pain relieving at the end of treatment (OR=3.08, 95%CI 2.30 to 4.12, P lt;0.000 01), the effectiveness rate of pain relieving two weeks after treatment (OR=3.39, 95%CI 2.52 to 4.56, P lt;0.000 01), the quality of life (OR=2.74, 95%CI 1.66 to 4.52, P lt;0.000 01) and the ability of movement (OR=2.96, 95%CI 2.16 to 4.05, P lt;0.000 01). Zoledronic acid combined with radiotherapy also reduced the incidence of new bone metastasis (OR=0.21, 95%CI 0.10 to 0.45, P lt;0.000 1) and the incidence rate of bone-related events (OR=0.17, 95%CI 0.03 to 0.92, P=0.04). The adverse reactions of zoledronic acid combined with radiotherapy such as fever (OR=11.92, 95%CI 6.31 to 22.48, P lt;0.000 01) and hypocalcaemia (OR=8.82, 95%CI 1.61 to 48.36, P=0.01), significantly increased.
Conclusion 　Compared with radiotherapy alone, zoledronic acid combined with radiotherapy can relieve bone metastatic pain, effectively enhance patients’ ability of movement, improve quality of life, and decrease new bone metastasis and the occurrence of bone-related events.

Citation： SHI Hongping,ZHANG Qiuning,LIU Guoqing,ZHANG Zhigang,WANG Daoying,LIU Xiaofeng,WANG Xiaohu. Zoledronic Acid Combined with Radiotherapy for Bone Metastases of Malignant Tumor: A Meta-Analysis. Chinese Journal of Evidence-Based Medicine, 2013, 13(7): 858-867. doi: 10.7507/1672-2531.20130152 Copy

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14.	杜联江, 李量, 蔡英全, 等. 唑莱膦酸配合放疗治疗骨转移疗效观察. 现代肿瘤医学, 2008, 16(5): 824-825.
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16.	王勇平, 郑安梅, 尹自飞, 等. 唑来膦酸联合放疗治疗脊柱转移瘤. 生物骨科材料与临床研究, 2011, 8(5): 16-19.
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18.	唐鑫, 汪俊谷, 王薏, 等. 唑来膦酸联合放疗治疗骨转移癌的临床观察. 西南国防医药, 2010, 20(2): 171-172.
19.	刘杰, 姜迎宵. 放疗联合唑来膦酸治疗恶性肿瘤骨转移疼痛的临床观察. 潍坊医学院学报, 2008, 30(3): 260-261.
20.	宁忠华, 裴红蕾, 黄谨, 等. 放疗联合唑来磷酸治疗转移性骨痛的临床研究. 现代肿瘤医学, 2007, 15(12): 1843-1846.
21.	王明智, 杨开华, 刘爱宁, 等. 放疗加唑来磷酸治疗骨转移瘤镇痛的临床疗效. 中国医院药学杂志, 2006, 26(10): 1267-1268.
22.	薛铮, 陈亚堃, 钱钧强, 等. 放疗联合唑来膦酸治疗恶性肿瘤骨转移的随机对照研究.西北药学杂志, 2012, 27(2): 162-163.
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24.	任锦霞, 王小虎, 赵林, 等. 放疗联合唑来膦酸治疗骨转移癌的疗效观察. 兰州大学学报(医学版), 2009, 35(3): 64-67.
25.	曹辉, 单硕, 周光, 等. 唑来膦酸合并放射治疗骨转移癌临床研究. 中国疼痛医学杂志, 2006, 12(1): 14-17.
26.	刘欣红. 唑来膦酸联合放疗治疗恶性肿瘤骨转移的疗效观察. 现代肿瘤医学, 2011, 19(7): 1412-1414.
27.	陈达桂, 李桂生, 黄海欣, 等. 唑来膦酸联合放疗治疗骨转移癌的临床观察. 中国现代医生, 2009, 47(9): 67-68.
28.	曹小飞, 陈龙华, 李启生, 等. 放疗联合唑来膦酸治疗骨转移癌的疗效观察. 广东医学, 2007, 28(3): 468-470.
29.	周江云. 单纯放疗与放疗联用唑来膦酸治疗骨转移癌疗效比较. 现代肿瘤医学, 2012, 20(8): 1693-1694.
30.	胡云峰, 雷侠. 单纯放疗与放疗联合唑来膦酸治疗骨转移瘤临床观察. 现代肿瘤医学, 2008, 16(1): 112-113.
31.	邓杰球, 何凯, 张坤强, 等. 唑来膦酸联合放疗治疗骨转移性癌痛的疗效观察. 中国医药导报, 2009, 6(12): 65-66.
32.	蒋晓东, 宋大安, 吴瑾, 等. 大分割放疗联合唑来膦酸治疗肺癌骨转移的临床疗效观察. 临床肺科杂志, 2007, 12(9): 913-914.
33.	熊林, 孟以秀. 放疗联合唑来膦酸治疗骨转移癌42例疗效分析. 重庆医学, 2009, 38(12): 1520-1521.
34.	谭章华, 张敏, 程伟, 等. 唑来膦酸同步放疗治疗前列腺癌骨转移疗效观察. 齐齐哈尔医学院学报, 2012, 33(3): 321-322.
35.	郑卫红,李旭,陈智,等.唑来膦酸联合放疗治疗骨转移癌效果观察. 中国综合临床, 2008, 24(12): 1262-1264.
36.	Zaghloul MS, Boutrus R, El-Hossieny H, et al. a prospective, randomized, placebo-controlled trial of zoledronic acid in bone metastatic bladder cancer. Int J Clin Oncol, 2010, 15(4): 382-389.
37.	Mehrotra B. Safety profile ofintravenous bisphosphonates. Semin Oncol, 2007, 34(6 Suppl4): 24-27.
38.	徐燮渊, 俞受程. 现代肿瘤放射治疗学. 西安: 人民军医出版社, 2000: 709-711.
39.	Coleman RE, Purohit OP. Osteoclast inhibition for the treatment of bone metastases. Cancer Treat Rev, 1993, 19(1): 79.
40.	方嘉华. 唑来膦酸联合放疗治疗骨转移癌的疗效观察. 安徽医学, 2007, 28(6): 517-518.
41.	殷蔚伯, 谷铣之. 肿瘤放射治疗学. 北京: 中国协和医科大学出版社, 2004: 1089 -1090.
42.	Wu JS, Wong R, Johnston M, et al. Meta - analysis of dose -fractionradiotherapy trials for the palliation of painful bone metastases. Int J Radiat Oncol Biol Phys, 2003, 55(3): 594.
43.	Coleman RE. Bisphosphonates: clinical experience. Oncologist, 2004, 9(4): 14-27.
44.	张娟, 李青峰, 龚先齐. 注射用唑来膦酸治疗恶性肿瘤骨转移性疼痛67 例临床观. 现代肿瘤医学, 2010, 18(10): 2044-2046.
45.	Dewar JA. Managing metastatic bone pain. BMJ, 2004, 329(7470): 812-813.

1. Wood house EC, Chuaqui RF, Liotta LA. General mechanisms of metastasis. Cancer, 1997, 80(8 Suppl): 1529.
2. 殷蔚伯. 肿瘤放射治疗学. 北京: 中国协和医科大学出版社, 2008.
3. 王若峥, 张国庆. 肿瘤放射治疗学. 北京: 科学出版室, 2010.
4. Yu SY, Jiang ZF, Zhang L, et al. Chinese expert consensus statement on clinical diagnosis and treatment of malignant tumor bone metastasis and bone related diseases. Chinese-German J Clin Oncol, 2010, 9(1): 1-12.
5. Costa L, Harper P, Coleman RE, et al. Anticancer evidence for zoledronic acid across the cancer continuum. Crit Rev Oncol Hematol, 2011, 77(1): S31-37.
6. Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.0 Avaliable from: www.cochrane-handbook.org, 2010-10-18.
7. Revi Manager. The Cochrane Collaboration.Copenhagen: The Nordic Cochrane Centre, 2008.
8. 李增云, 马庆彤, 任晓, 等. 唑来膦酸联合放疗治疗骨转移性疼痛的临床观察. 四川肿瘤防治, 2006, 19(3): 208-209.
9. 秦玲, 张华, 潘桂华, 等. 唑来膦酸联合放疗治疗恶性肿瘤骨转移的临床疗效观察. 实用癌症杂志, 2008, 23(4): 410-411.
10. 谭换明, 杨永宏. 唑来膦酸联合放疗治疗骨转移癌的疗效观察. 中国社区医师(医学专业半月刊), 2009, 11(9): 31-32.
11. 狄剑士, 刘欣, 毕经旺, 等. 唑来膦酸联合放疗治疗骨转移癌疗效观察. 人民军医, 2007, 50(11): 674-675.
12. 朱琪伟, 谢国栋, 顾红芳, 等. 唑来膦酸联合放疗治疗骨转移癌疗效观察. 山东医药, 2007, 47(32): 83-84.
13. 龙建林, 易全会, 任章霞, 等. 唑来膦酸联合放射治疗42例骨转移性癌的临床观察. 西部医学, 2010, 22(7): 1224-1226.
14. 杜联江, 李量, 蔡英全, 等. 唑莱膦酸配合放疗治疗骨转移疗效观察. 现代肿瘤医学, 2008, 16(5): 824-825.
15. 李咏梅, 王伟, 陈素琼, 等. 唑来膦酸钠联合放疗治疗骨转移癌临床观察. 宁夏医科大学学报, 2009, 31(2): 227-228.
16. 王勇平, 郑安梅, 尹自飞, 等. 唑来膦酸联合放疗治疗脊柱转移瘤. 生物骨科材料与临床研究, 2011, 8(5): 16-19.
17. 吴瑾, 周莉华, 蒋晓东, 等. 唑来膦酸联合放疗治疗骨转移癌临床研究. 实用癌症杂志, 2007, 22(4): 404-406.
18. 唐鑫, 汪俊谷, 王薏, 等. 唑来膦酸联合放疗治疗骨转移癌的临床观察. 西南国防医药, 2010, 20(2): 171-172.
19. 刘杰, 姜迎宵. 放疗联合唑来膦酸治疗恶性肿瘤骨转移疼痛的临床观察. 潍坊医学院学报, 2008, 30(3): 260-261.
20. 宁忠华, 裴红蕾, 黄谨, 等. 放疗联合唑来磷酸治疗转移性骨痛的临床研究. 现代肿瘤医学, 2007, 15(12): 1843-1846.
21. 王明智, 杨开华, 刘爱宁, 等. 放疗加唑来磷酸治疗骨转移瘤镇痛的临床疗效. 中国医院药学杂志, 2006, 26(10): 1267-1268.
22. 薛铮, 陈亚堃, 钱钧强, 等. 放疗联合唑来膦酸治疗恶性肿瘤骨转移的随机对照研究.西北药学杂志, 2012, 27(2): 162-163.
23. 胡莉钧, 李毅, 聂斌, 等. 放疗联合唑来膦酸姑息性治疗骨转移癌86例疗效分析. 中国医药指南, 2011, 09(16): 99-100.
24. 任锦霞, 王小虎, 赵林, 等. 放疗联合唑来膦酸治疗骨转移癌的疗效观察. 兰州大学学报(医学版), 2009, 35(3): 64-67.
25. 曹辉, 单硕, 周光, 等. 唑来膦酸合并放射治疗骨转移癌临床研究. 中国疼痛医学杂志, 2006, 12(1): 14-17.
26. 刘欣红. 唑来膦酸联合放疗治疗恶性肿瘤骨转移的疗效观察. 现代肿瘤医学, 2011, 19(7): 1412-1414.
27. 陈达桂, 李桂生, 黄海欣, 等. 唑来膦酸联合放疗治疗骨转移癌的临床观察. 中国现代医生, 2009, 47(9): 67-68.
28. 曹小飞, 陈龙华, 李启生, 等. 放疗联合唑来膦酸治疗骨转移癌的疗效观察. 广东医学, 2007, 28(3): 468-470.
29. 周江云. 单纯放疗与放疗联用唑来膦酸治疗骨转移癌疗效比较. 现代肿瘤医学, 2012, 20(8): 1693-1694.
30. 胡云峰, 雷侠. 单纯放疗与放疗联合唑来膦酸治疗骨转移瘤临床观察. 现代肿瘤医学, 2008, 16(1): 112-113.
31. 邓杰球, 何凯, 张坤强, 等. 唑来膦酸联合放疗治疗骨转移性癌痛的疗效观察. 中国医药导报, 2009, 6(12): 65-66.
32. 蒋晓东, 宋大安, 吴瑾, 等. 大分割放疗联合唑来膦酸治疗肺癌骨转移的临床疗效观察. 临床肺科杂志, 2007, 12(9): 913-914.
33. 熊林, 孟以秀. 放疗联合唑来膦酸治疗骨转移癌42例疗效分析. 重庆医学, 2009, 38(12): 1520-1521.
34. 谭章华, 张敏, 程伟, 等. 唑来膦酸同步放疗治疗前列腺癌骨转移疗效观察. 齐齐哈尔医学院学报, 2012, 33(3): 321-322.
35. 郑卫红,李旭,陈智,等.唑来膦酸联合放疗治疗骨转移癌效果观察. 中国综合临床, 2008, 24(12): 1262-1264.
36. Zaghloul MS, Boutrus R, El-Hossieny H, et al. a prospective, randomized, placebo-controlled trial of zoledronic acid in bone metastatic bladder cancer. Int J Clin Oncol, 2010, 15(4): 382-389.
37. Mehrotra B. Safety profile ofintravenous bisphosphonates. Semin Oncol, 2007, 34(6 Suppl4): 24-27.
38. 徐燮渊, 俞受程. 现代肿瘤放射治疗学. 西安: 人民军医出版社, 2000: 709-711.
39. Coleman RE, Purohit OP. Osteoclast inhibition for the treatment of bone metastases. Cancer Treat Rev, 1993, 19(1): 79.
40. 方嘉华. 唑来膦酸联合放疗治疗骨转移癌的疗效观察. 安徽医学, 2007, 28(6): 517-518.
41. 殷蔚伯, 谷铣之. 肿瘤放射治疗学. 北京: 中国协和医科大学出版社, 2004: 1089 -1090.
42. Wu JS, Wong R, Johnston M, et al. Meta - analysis of dose -fractionradiotherapy trials for the palliation of painful bone metastases. Int J Radiat Oncol Biol Phys, 2003, 55(3): 594.
43. Coleman RE. Bisphosphonates: clinical experience. Oncologist, 2004, 9(4): 14-27.
44. 张娟, 李青峰, 龚先齐. 注射用唑来膦酸治疗恶性肿瘤骨转移性疼痛67 例临床观. 现代肿瘤医学, 2010, 18(10): 2044-2046.
45. Dewar JA. Managing metastatic bone pain. BMJ, 2004, 329(7470): 812-813.

Chinese Journal of Evidence-Based Medicine

Zoledronic Acid Combined with Radiotherapy for Bone Metastases of Malignant Tumor: A Meta-Analysis

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